Apparatus useful in suppression of spermatogenesis

ABSTRACT

Apparatus useful in suppressing spermatogenesis in human males by applying ultrasonic vibrations to the testes. More particularly, apparatus useful in suppressing spermatogenesis by sonicating male testes including a cup for immersing the testes in an ultrasonic coupling agent and an ultrasonic applicator for applying ultrasonic vibrations thereto.

This invention relates to apparatus useful in the suppression ofspermatogenesis in human males with ultrasound.

Recently, there has been increasing interest in developing a malecontraceptive. Ideally such a contraceptive would cause temporary orpermanent sterility selectively as desired without affecting a man's sexdrive, his sex characteristics or general health. Spurring this interesthas been a growing concern over population growth, coupled with fearsthat long-term use of birth control pills or intrauterine devices may beharmful to some women.

Despite some progress, development of a male antifertility agent hasbeen slow. Presently, the most promising pharmaceutical approach to atemporary male contraceptive combines synthetic testosterone with ananalogue called danazol. At the most effective dosage, sperm productionstops entirely or drops to a very low level but not without certain sideeffects. More particularly, testosterone sometimes causes a rise inblood fats which increases the risk of heart attack.

Up until now, vasectomy has been the only non-pharmaceutical malecontraceptive other than condoms, which most couples reject asunreliable and cumbersome. A vasectomy is a surgical procedure whichconsists of cutting the tube which carries sperm from the testes to thepenis and which requires skilled personnel and an anesthetic to perform.It is usually not reversible, is painful and involves the usual risksassociated with surgery. This method is also frequently accompanied bycomplications such as hematomata, edema, pain on ejaculation, spermgranulomata and vas recanalization. It is also feared that vasectomy canproduce certain adverse long-term effects.

More particularly, it has been found that vasectomy in male rats causesreduction in testis weight, reduction of testosterone in the blood, bodyweight gain and fat deposits and partial impairment of drug-metabolizingenzymes in the liver. Fed. Proc. Vol. 33, No. 3, March 1974. Since therehave been no long-term studies on the effect of vasectomy on men, thereis concern that humans may experience the same adverse effects as ratsundergoing this procedure.

The ability of heat to suppress spermatogenesis has been known for manyyears. Researchers in 1922 were probably the first to suggest that thedamage to the seminiferous epithelium of cryptorchid testes is theresult of exposure of such testes to intra-abdominal temperature, whichis higher than the intrascrotal temperature. J. Anat. 56:98. Thissuggestion has been supported by observations that intrascrotal testesexposed experimentally to elevated temperatures respond with rapiddegeneration of the seminiferous epithelium. Japan Med. World 3:160-163(1923), Am. J. Anat. 34:373-380 (1924) and J. Exp. Zool. 49:459-463(1927).

While the effect of heat on the testes was generally known, it had notbeen considerated for its contraceptive potential before the research ofwhich the present invention is a portion. To this end, several sourcesof heat including hot water, infrared, microwavs and ultrasound weretried for their contraceptive potential on male rats. On the basis ofthese tests, it was found that infrared was more effective than hotwater but less so than microwaves and ultrasound. Moreover, infraredtreatment caused some skin drying and burning. Microwaves, on the otherhand, unlike ultrasound, required elaborate shielding to protect againstblinding and other tissue damage. Based on ease of treatment andeffectiveness, ultrasound was found to be the preferred method oftreatment. These tests were reported in Contraception, Vol. 11, No. 5,May 1975.

The effect of ultrasound on the testes of other laboratory animals hasalso ben tested with similar results to that in rats. These tests arereported in a paper presented to the American Fertility Society in April1976.

In view of the above, among the several objects of the present inventionmay be noted the provision of apparatus useful in suppressingspermatogenesis in human males with ultrasound. This apparatus providesfor the controlled application of ultrasonic vibrations to the testes ofhuman males in such a way to cause temporary or permanent sterilityselectively as desired without affecting the subject's sex drive, hissex characteristics or general health. Other objects and features willbe in part apparent and in part pointed out hereinafter.

This invention accordingly comprises the apparatus hereinafterdescribed, the scope of the invention being indicated in the subjoinedclaims.

In accordance with the present invention, apparatus for the treatment ofthe testes of human males with ultrasonic vibrations is provided. Moreparticularly, apparatus for immersing the testes in an ultrasoundcoupling agent contained in a suitable vessel. The apparatus thenprovides for treatment of the immersed testes with ultrasonic vibrationsfrom an ultrasonic applicator which is constructed so that it can beplaced in direct contact with the coupling agent in the vessel or sothat its vibrations are passed thereto through the walls of the vessel.

In the accompanying drawings, several embodiments of the apparatus ofthe invention are illustrated.

FIG. 1 is an exploded perspective view of a chair for use in applyingultrasound to human testes;

FIG. 2 is a side elevational view of the chair shown in FIG. 1; shownpartly in section;

FIG. 3 is a front elevational view of the chair shown in FIG. 1;

FIG. 4 is an enlarged perspective view of the adjustable holder for usein holding the cup during the application of ultrasound to human testes;

FIG. 5 is a perspective view of a stand for use in applying ultrasoundto human testes;

FIG. 6 is a longitudinal cross-sectional view taken along line 6--6 inFIG. 5;

FIG. 7 is a side elevational view of a cup for use in applyingultrasound to human testes;

FIG. 8 is a longitudinal cross-sectional view taken along line 8--8 inFIG. 9;

FIG. 9 is a horizontal cross-section view taken along line 9--9 in FIG.8;

FIG. 10 is a side elevational view of another cup for use in applyingultrasound to human testes; and

FIG. 11 is a longitudinal cross-sectional view of the cup shown in FIG.10.

Reference numeral 10 refers to a chair constructed according to thepresent invention, said chair having a seat 12 with an elongatedU-shaped notch 14 in the front edge thereof. Notch 14 is centrallylocated along the front edge so that when a man is seated on chair 10with his legs spread that his testicles hang freely through the notch.As best seen in FIG. 2, the testicles of the subject so positioned arereceived in cup 16 for treatment as hereinafter described.

Cup 16 is supported by a bracket assembly 18 which is mounted on aslidable drawer shelf 20. Shelf 20 is suported by strips 22 which areattached to the underside of seat 12. Strips 22 extend from adjacent thebase of U-shaped notch 14 towards the back of seat 12 and are positionedgenerally parallel to the lateral edges of the notch.

Shelf 20 is wider than notch 14 and is received in opposing rabbetedlateral edges 24 of strips 22. Rabbets 24 are dimensioned so that shelf20 is slidable therealong without unnecessary looseness. As shown, shelf20 is longer than notch 14 so that shelf 20 may be extended beyond theleading edge of chair seat 12 as well as retracted beyond the bottom ofnotch 14.

As best seen in FIG. 1, bracket assembly 18 is attached adjacent theleading edge of shelf 20 by linkage 26. Linkage 26 has two upstandingapertured ears 28 extending down from the underside of shelf 20 forpivotal attachment at 30 to linkage 32. Linkage 32 is like linkage 26and includes two upstanding apertured ears 34 for pivotal attachment at36 to apertured arm 38 of holder 40. Pivotal linkags 30 and 36 areadjusted so that bracket assembly 18 remains in a selected position onceplaced therein. Holder 40 is cylindrical in shape and is dimensioned toreceive cup 16. It is provided with a set screw 42 to prevent cup 16from being unseated therefrom.

As will be understod, bracket assembly 18 provides for verticaldisplacement of cup 16 from the plane of chair seat 12 and formaintaining the cup in level condition. Whereas, shelf 20 provides fordisplacement of cup 16 with respect to the leading edge of the seat. Thechair so adjustable is adaptable to the anatomy of the particularpatient.

Another embodiment of the present invention is shown in FIG. 5. In thisfigure, reference numeral 44 refers to a stand having a base 46 and anupstanding leg 48 attached thereto. As shown, leg 48 is tubular incross-section and is tipped with a cap 50.

An arm 52 is adjustably attached to leg 48. The distal end 54 of arm 52terminates in a holder 56 for cup 58. Holder 56 and cup 58 are similarin function to holder 40 and cup 16 and may be identical thereto. Theproximal end 60 of arm 52 is received in a clamp 62. As best seen inFIG. 6, clamp 62 includes a ball-shaped housing 64 which is passed alongits diameter over leg 48. Housing 64 is tapped to receive a threadedshaft 66 associated with handle 68. When shaft 66 is moved to the left,as viewed in FIG. 6, in response to movements of handle 68, the forwardend of the shaft bears against spring biased member 70 which acts as abrake on leg 48. Spring biased member 70 is provided so that clamp 62does not mar leg 48 when tightened thereon. As will be understood, clamp62 provides for vertical displacement of cup 58 to adjust to the anatomyof the standing patient.

Cups 16 and 58 are preferably formed of methyl methacrylate or ofsimilar material and are provided in a range of sizes. If three cups areprovided as follows, it has been found that the testes of most subjectsare accommodated: Cup A having an inside diameter of 4.9 cm and a depthof 4.5 cm, Cup B having an inside diameter of 6.9 cm and a depth of 5.5cm and Cup C having an inside diameter of 8.2 cm and a depth of 5.8 cm.Cups 16 and 58 are preferably provided with a rubber cushion 71 aroundtheir rims.

As shown in FIGS. 7-9, cup 16 includes a cylindrical sidewall 72 whichis sealed on one end to a bottom wall 74. Bottom wall 74 has an aperture76 centrally located therein, said aperture having a recess 78 in therim thereof. An ultrasound applicator 80 is sealed in aperture 76 withan O-ring 82 which is fitted in recess 78 provided therefor. Ultrasoundapplicator 80 includes a transducer (not shown) within a housing 84which protects the transducer from the contents of cup 16.

As shown in FIGS. 10 and 11, cup 58, like cup 16, includes a cylindricalsidewall 86 which is sealed at one end to bottom wall 88. Ultrasoundapplicator 90 includes a transducer 92 which is cemented or otherwisesuitably affixed to the underside of bottom wall 88 and is protected bycap 94 which is slip fitted over the bottom of the cup.

Since ultrasound does not transmit through air, a coupling agent must beprovided in cups 16 and 58 to provide coupling between the ultrasonicapplicator and the testes to be treated. The particular coupling agentselected is preferably non-staining, non-irritating and slowevaporating. For this purpose, the agent may be water or water mixedwith other materials. Other coupling agents such as oils or the like arealso contemplated.

In use when the subject is ready for treatment, a cup is selected,filling with coupling agent and the patient is comfortably positioned sothat his testicles are immersed therein. When chair 10 or stand 44 isused to hold the cup, this condition is readily accomplished byappropriate adjustments of the equipment to the patient as abovedescribed.

The length of the treatment, output frequency of the ultrasonicgenerator 100 coupled to ultrasound applicator 80 or 90 and power levelat the applicator surface will vary in the individual case and is up tothe treating physician. It has been found that generally the greater theenergy applied to the testes, the more permanent is the suppression ofspermatogenesis. Hence, the practical range of power depends upon thepurpose of the treatment. Very high power levels, however, should beavoided to prevent burning the subject's skin. The most practical rangeis from about 0.25 to about 3 watt/cm² but the power level may go aboveor below that range. A preferred range is from about 0.5 to about 2watt/cm² and a more preferred range is from about 0.5 to about 1watt/cm².

Usually the frequency of the ultrasonic vibrations is within the rangefrom about 500 to about 5000 KHZ. A preferred range is from about 500 toabout 2500 KHZ and a particularly effective setting is 1100 KHZ ± 10KHZ. Within the above mentioned ranges, the suppression ofspermatogenesis tends to be more permanent with increasing frequency,other treatment variables remaining constant.

The length and number of treatments also has an effect on the degreethat spermatogenesis is suppressed. Usually the treatment is within therange from about 3 to about 15 min., but by varying the other treatmentconditions, the duration can be increased or shortened as desired.

It has been found that spermatogenesis can be suppressed by treatment at1100 KHZ ± 10 KHZ with 1 watt/cm² for 10 min. The degree of suppressionis determined by a sperm count. Since the normal count is about 50 toabout 150 million/cc, a man with a count below about 20 million isregarded as infertile. If the subject's sperm count is too high afterthe first treatment, treatment as described above is repeated, howeverpreferably after a wait of about 2 weeks. Again, a sperm count is takenand the treatment continued until the desired degree of suppression,either temporary or permanent, has been accomplished. The number oftreatments to reduce the sperm count to zero for complete sterilization,if desired, depends upon the subject's condition, including such factorsas his age and general health.

The following examples illustrate use of the apparatus described above.

EXAMPLE 1

A human patient with carcinoma of the prostate was selected andcomfortably seated on chair 10. A cord (not shown) was loosely tiedaround the base of the scrotum to prevent displacement of the testesduring treatment.

A cup 16 was selected of a size to accommodate the testicles of thesubject. It was filled with water and the patient's testicles immersedtherein. Cup 16 was then positioned by manipulation of bracket assembly18 and drawer shelf 20 so that the testicles approached within 1/4 to1/2 inch of ultrasound applicator 80.

The transducer (not shown) in applicator 80 measured 11 cm² and wasconnected to an ultrasonic generator manufactured by WhitewaterElectronics, Inc. This generator had a frequency of 1100 KHZ ± 10 KHZ, acontinuous power output of 0 to 35 watts and was set so that theeffective power level at applicator 80 was 1 watt/cm².

The patient's testes were treated with 1 watt/cm² of ultrasound for 10minutes while he was seated on chair 10 as aforementioned.

Two weeks after treatment, the patient underwent orchiectomy and histestes were taken. Part of the testes were prepared for examination bylight microscopy by immersing them in Bovin's solution for 48 hours. Thetestes were then transferred to 70% ethanol and embedded in paraplast.Four micron sections were cut, stained with hemotoxylin and eosin andexamined under a light microscope.

Another part of the testes were prepared for examination by electronmicroscopy by cutting the seminiferous tubules into 3 mm lengths. Thetubules were fixed first with 2% osmium tetroxide in 0.1 M phosphatebuffer at pH 7.4 for 1 hour. This was followed by post-fixation in 3%glutaraldehyde in 0.1 M phosphate buffer at pH 7.4 for 1 hour.

The tubules were dehydrated with ethanol and embedded in Epon 812according to standard procedure. When the blocks hardened, thin sectionswere stained with uranyl acetate for 15 min. followed by lead citratefor 5 min. These sections were examined under an electron microscope.

The results from light and electron microscopy showed that there were nosperm or spermatids in the tubules but that the Lyding cell populationwas normal. The blood testosterone level was also found to be normal.

EXAMPLE 2

A second human patient with carcinoma of the prostate was treated asdescribed in Example 1 except that the ultrasonic generator was set sothat the effective power level at applicator 80 was 0.5 watt/cm². Twoweeks after treatment, the patient underwent orchiectomy and his testeswere examined as in Example 1.

The results from light and electron microscopy showed that there were nosperm in the tubules and about a 50% reduction in the number ofspermatid. The Lyding cell population was normal as was the bloodtestosterone level.

EXAMPLE 3

A third human patient with carcinoma of the prostate was treated asdescribed in Example 1. Two days after treatment, the patient underwentorchiectomy and his testes were examined as in Example 1.

The results from light and electron microscopy showed that the membranesof the advanced testicular cells (spermatid and spermatocytes) had losttheir integrity and exhibited very irregular shapes. Their plasmamembranes had developed leaks and some cytoplasm had escaped into theinterstitial area. The spermatogonia and sertoli cells, however,remained intact indicating that the destruction of sperm and spermatidwas temporary and that the tubules were capable of spermatogenesis.

In view of the above, it will be seen that the several objects of theinvention are achieved and other advantageous results attained.

As various changes could be made in the above described apparatuswithout departing from the scope of the invention, it is intended thatall matters contained in the above description or shown in theaccompanying drawings shall be interpreted as illustrative and not in alimiting sense.

What is claimed is:
 1. A treatment device for a selected human malehaving a scrotum with testes comprising a vessel containing a couplingagent, an ultrasonic transducer means in operative relationship withsaid vessel to propagate continuous ultrasonic vibrations throughout thecoupling agent, said vessel sized to receive and immerse in the couplingagent only the scrotum of the selected human male, ultrasonic generatormeans for generating continuous power to said transducer means to allowthe transducer means to propagate said continuous vibrations, whereinsaid ultrasonic transducer means oscillate at a frequency between about500 and about 5000 KHZ, support means for displacing the vesselvertically and maintaining the vessel in level condition while saidscrotum is immersed in the coupling agent and said support means beingfurther for displacing the vessel horizontally thereby adapting thevessel for alignment with the scrotum of the selected human male and forreceipt and immersion of said scrotum.
 2. The treatment device accordingto claim 1 wherein said ultrasonic transducer means oscillate at afrequency between about 500 and about 2500 KHZ.
 3. The treatment deviceaccording to claim 2 wherein said ultrasonic transducer means have apower level between about 0.25 watt/cm² and about 3 watt/cm².
 4. Thetreatment device according to claim 3 wherein said ultrasonic transducermeans have a power level between about 0.5 watt/cm² and about 2watt/cm².
 5. The treatment device according to claim 4 wherein saidultrasonic transducer means have a power level between about 0.5watt/cm² and about 1 watt/cm².
 6. The treatment device according toclaim 5 wherein said ultrasonic transducer means oscillate at afrequency of 1100 KHZ ± 10 KHZ.
 7. The treatment device according toclaim 1 which further comprises a chair having a seat and a front edgetowards which the selected human male is faced when seated for treatmenton the chair, said support means being mounted on said chair seat withthe vessel adjacent the front edge of the chair.
 8. The treatment deviceaccording to claim 7 wherein the chair has a back and a notch formed inthe front edge of the chair, said notch aligned and freely accommodatingthe scrotum of the selected human male when seated on the chair fortreatment, said notch extending substantially midway between the frontedge of the chair and the back, said support means being mounted on anunderside of the chair seat adjacent the notch.
 9. The treatment deviceaccording to claim 1 and which further comprises a stand, the supportmeans including an arm, said arm being mounted on said stand, said armbeing vertically and horizontally adjustable on said stand.